Bone Marrow Transplantation, (1998) 21, 955–956  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http:/ / www.stockton-press.co.uk/ bmt Case report Achievement of complete cytogenetic remission after two very low- dose donor leucocyte infusions in a patient with extensive cGVHD relapsing in accelerated phase post allogeneic BMT for CML SL Rahman 1 , P Mahendra 1 , E Nacheva 1 , P Sinclair 1 , J Arno 2 and RE Marcus 1 1 Bone Marrow Transplant Unit and 2 Department of Pathology, Addenbrooke’s NHS Trust, Cambridge, UK Summary: We report the case of a 55-year-old female who despite having developed extensive chronic graft-versus-host disease (GVHD), relapsed 35 months after a T cell- replete sibling donor bone marrow transplant for Phila- delphia-positive chronic myeloid leukaemia (Ph CML). She achieved complete cytogenetic remission after dis- continuation of cyclosporin A and administration of two low-dose donor leucocyte infusions (DLI 1 × 10 6 and 5 × 10 6 CD3 + cells/kg). Eighteen months after the first infusion she remains well and in complete cytogenetic remission with a normocellular marrow and no exacer- bation of GVHD. Keywords: chronic myeloid leukaemia; allogeneic bone marrow transplantation; graft-versus-host disease; donor leucocyte infusion Case report In November 1992, a 53-year-old female with Ph CML in first chronic phase underwent an allogeneic bone marrow transplant from an HLA-compatible female sibling donor. Conditioning consisted of total body irradiation (TBI), 1400cGy in eight fractions, and cyclophosphamide 120 mg/kg. As prophylaxis against the GVHD she received cyclosporin A and short-course methotrexate (8 mg/m 2 on days + 2, + 4, + 8 and + 12). She engrafted neutrophils on day + 24, but went on to develop grade II skin GVHD, which was treated with intravenous methylprednisolone. She was discharged home on day + 46 on a reducing dose of steroids with a blood count as follows: Hb 10.7 g/dl, WBC 3.5 × 10 9 /l, platelets 168 × 10 9 /l. The skin GVHD pro- gressed to extensive chronic GVHD affecting the skin, oral mucosa and vagina. This was treated with prednisolone from 4 months to 31 months post BMT, azathioprine from 7 months to 16 months post BMT and thalidomide from 18 months to 25 months post BMT. The azathioprine and thalidomide were discontinued because of myelosuppres- Correspondence: Dr RE Marcus, Box 234, Dept of Haematology, Adden- brooke’s NHS Trust, Hills Rd, Cambridge CB2 2QQ, UK Received 3 September 1997; accepted 13 November 1997 sion and severe neurological side-effects, respectively. Cyclosporin A was discontinued at 9 months post BMT. It was re-started at 24 months after BMT due to failure to control cGVHD with the other agents. Bone marrow cytogenetics at 7 months post BMT showed 100% Ph negativity and cytogenetics done at 24 months post BMT failed to grow. At 33 months post trans- plant her blood count was as follows: Hb 12.2 g/dl, WBC 3.2 × 10 9 /l, platelets 271 × 10 9 /l; bone marrow cytogenetics showed 100% Ph negativity. Two months later at routine follow-up the platelet count had risen to 613 × 10 9 /l. A bone marrow examination showed that 40% of the meta- phases were Ph+ ve, with deletions of 20q- and 7p-. Cyclo- sporin A was discontinued, but 2 months later (ie 37 months post BMT), the platelet count had risen to 1500 × 10 9 /l, and bone marrow cytogenetics confirmed 100% Ph positivity. She was started on hydroxyurea. In an attempt to induce Ph negativity without exacerbating her GVHD we infused an initial ‘test-dose’ of 1 × 10 6 CD3+ ve donor leucocytes/kg. Two weeks post DLI the platelet count remained elevated at 1700 × 10 9 /l and anagrelide was substituted for the hydroxyurea. Four weeks post first DLI (38 months post BMT), a second DLI of 5 × 10 6 CD3+ ve cells/kg was given. One week after this second infusion, the patient became pancytopenic (Hb 10.8 g/dl, WBC 1.5 × 10 9 /l, platelets 48 × 10 9 /l), and a trephine biopsy showed a severely hypoplastic marrow. Cytogenetics revealed 20% Philadelphia negativity. Anagrelide was dis- continued after a total of 5 weeks. Four months after the first DLI her blood count was as follows: Hb 13.1 g/dl, WBC 3.4 × 10 9 /l, platelets 177 × 10 9 /l; cytogenetics failed to grow but FISH analysis on interphase cells showed that 9/10 cells were bcr/abl positive. Her trephine biopsy remained hypoplastic. Eight months post first DLI her blood count remained stable (Hb 12.4 g/dl, WBC 3.2 × 10 9 /l, platelets 173 × 10 9 /l); cytogenetics analysis failed and her trephine biopsy showed evidence of recovering hypoplasia. Eighteen months post first DLI she continues to have a normal blood count, cytogenetics now show 100% Ph negativity and her trephine biopsy is normo- cellular. She remains well with no acute GVHD or exacer- bation of her previous cGVHD.